Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model

Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some na?ve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.     

Immunosuppressive drugs and highly active antiretroviral therapy: pharmacokinetic interactions

The development of highly active antiretroviral therapy has greatly improved HIV-infected patient survival. However, the increased life expectancy associated with the management of opportunistic infections might favour the onset of severe organic failure that could require organ transplantation. The use of immunosuppressive drugs in association with antiretroviral therapy will generate pharmacodynamic and pharmacokinetic interactions. In this context, therapeutic drug monitoring is of great importance to improve therapeutic management of patients.     

Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant – a pilot study

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn’s disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.     

Current status of bone graft options for anterior interbody fusion of the cervical and lumbar spine

Anterior cervical discectomy and fusion (ACDF) and anterior lumbar interbody fusion (ALIF) are common surgical procedures for degenerative disc disease of the cervical and lumbar spine. Over the years, many bone graft options have been developed and investigated aimed at complimenting or substituting autograft bone, the traditional fusion substrate. Here, we summarise the historical context, biological basis and current best evidence for these bone graft options in ACDF and ALIF.     

Perineal colostomy: an alternative to avoid permanent abdominal colostomy: operative technique,results and reflection

Background

The most common injury to indicate definitive stoma is rectal cancer. Despite advances in surgical treatment, the abdominoperineal resection is still the most effective operation in radical treatment of malignancies of the distal rectum invading the sphincter and anal canal. Even with all the effort that surgeons have to preserve anal sphincters, abdominoperineal amputation is still indicated, and a definitive abdominal colostomy is necessary. This surgery requires patients to live with a definitive abdominal colostomy, which is a condition that modify body image, is not without morbidity and has great impact on the quality of life.

Aim

To evaluate the technique of abdominoperineal amputation with perineal colostomy with irrigation as an alternative to permanent abdominal colostomy.

Method

Retrospective analysis of medical records of 55 patients underwent abdominoperineal resection of the rectum with perineal colostomy in the period 1989-2010.

Results

The mean age was 58 years, 40 % men and 60 % women. In 94.5% of patients the indication for surgery was for cancer of the rectum. In some patients were made three valves, other two valves and in the remaining no valve at all. Complications were: mucosal prolapse, necrosis of the lowered segment and stenosis.

Conclusion

The abdominoperineal amputation with perineal colostomy is a good therapeutic option in the armamentarium of the surgical treatment of rectal cancer.     

Evaluating the safety and efficacy of the 1,440‐nm laser in the treatment of photodamage in Asian skin

Background and Objective

As the demand for diminished procedure‐associated downtime continues to increase, nonablative fractional laser resurfacing is becoming a more popular intervention in the progression of photoaging. Patients with pigmented skin and a mild degree of photodamage may be particularly suited for a less intensive laser treatment. In this study, we have evaluated the safety and efficacy of a low energy, low density 1,440‐nm fractional laser in the treatment of multiple signs of photoaging including dyspigmentation, wrinkling, tissue laxity, enlarged pores, and skin roughness in Asians.

Study Design/Materials and Methods

Ten Chinese subjects with Fitzpatrick skin types III–V and visible signs of photodamage participated in this study. Patients received four treatments at 2‐week intervals with a 1,440‐nm diode‐based fractional laser. Photographs were taken at baseline, 2 weeks after each of the first three treatments and 4 weeks after the final treatment. Images were evaluated independently by two physicians. Clinical improvement and adverse events were analyzed. Discomfort, heat sensation and overall patient satisfaction associated with the procedure were also quantified.

Results

In this prospective single‐arm study, signs of photoaging were examined after treatment with the 1,440‐nm laser. Here we show that a series of four treatments with this device produced a mild improvement in skin texture, pigmentation, and wrinkling. Changes in pore size and skin laxity failed to reach statistical significance. Immediate after‐effects of the procedure included erythema and edema which were transient and left no permanent sequela. A significant proportion of patients reported some degree of discomfort during the procedure despite use of a topical anesthetic. One patient developed a discrete, localized area of post‐inflammatory hyperpigmentation which completely resolved by the final follow up visit.

Conclusion

The low energy, low density nonablative 1,440‐nm fractional laser produces a mild improvement in select signs of photodamage after four treatments without any long‐term adverse effects. Lasers Surg. Med. 46:375–379, 2014. © 2014 Wiley Periodicals, Inc.     

Effect of Beetroot Juice Supplementation on Aerobic Response during Swimming

The beneficial effects of beetroot juice supplementation (BJS) have been tested during cycling, walking, and running. The purpose of the present study was to investigate whether BJS can also improve performance in swimmers. Fourteen moderately trained male master swimmers were recruited and underwent two incremental swimming tests randomly assigned in a pool during which workload, oxygen uptake (VO₂), carbon dioxide production (VCO₂), pulmonary ventilation (VE), and aerobic energy cost (AEC) of swimming were measured. One was a control swimming test (CSW) and the other a swimming test after six days of BJS (0.5l/day organic beetroot juice containing about 5.5 mmol of NO₃⁻). Results show that workload at anaerobic threshold was significantly increased by BJS as compared to the CSW test (6.3 ± 1 and 6.7 ± 1.1 kg during the CSW and the BJS test respectively). Moreover, AEC was significantly reduced during the BJS test (1.9 ± 0.5 during the SW test vs. 1.7 ± 0.3 kcal·kg⁻¹·h⁻¹ during the BJS test). The other variables lacked a statistically significant effect with BJS. The present investigation provides evidence that BJS positively affects performance of swimmers as it reduces the AEC and increases the workload at anaerobic threshold.     

Strain differences influence timing and magnitude of both acute and late inflammatory reactions after intratracheal instillation of an alkylating agent in rats

The acute pulmonary responses after exposure to sulfur and nitrogen mustards are well documented whereas the late pulmonary effects are not. With a novel focus on the immune system this paper investigate whether late phase pulmonary effects developed in rats exposed to the nitrogen mustard melphalan are linked to the acute responses and whether the reactions are genetically regulated. The DA rat strain was used to establish a lung exposure model. Five other inbred rat strains (PVG, PVG.1AV1, LEW, WF and F344) were compared within the model at selected time points. All rat strains displayed a biphasic pattern of leukocyte infiltration in the lungs, dominated by neutrophils 2 days after exposure and a second peak dominated by macrophages 29 days after exposure. The number of macrophages was higher in the DA rat compared with the other strains. The infiltration of lymphocytes in the lungs varied in both time of appearance and magnitude between strains. The quantity of collagen deposition in the lungs varied between strains at day 90; LEW and WF displayed high collagen content which coincided with an increased level of cytotoxic T cells. LEW further displayed an increased number of T helper cells and natural killer (NK) T cells in the lungs. The results in this study suggest there is a link between the development of lung fibrosis and high cytotoxic cell responses and that there is a genetic influence, as there are variations in acute and late adverse reactions between rat strains in both timing and magnitude. Copyright © 2013 John Wiley & Sons, Ltd.     

Parental smoking and risk of coeliac disease in offspring

OBJECTIVE: In adults, smoking seems to give protection against coeliac disease (CD). But, only one study has thus far investigated the association between maternal smoking during pregnancy and risk of CD in offspring. However, that study did not adjust for duration of exclusive breastfeeding, or look at passive smoking after birth. MATERIAL AND METHODS: The current study was part of a prospective cohort study of infants born between 1 October 1997 and 1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Data on smoking and exclusive breastfeeding were obtained through questionnaires distributed at infant birth and at 1 year of age. Coeliac disease was confirmed through small-bowel biopsy. Subgroup analyses were carried out according to maternal body mass index. RESULTS: Nine out of 53 (17%) children with CD as opposed to 1699 out of 15,344 (11.1%) non-coeliac children had mothers who had smoked during pregnancy (p = 0.172). Mothers who had smoked during pregnancy were hence not at increased risk of having a child with CD (OR = 1.64; 95% CI OR =0.80-3.37). Adjusting for duration of exclusive breastfeeding and the sex of infants in some 9585 children with data on exclusive breastfeeding lowered the OR for CD in mothers who smoked (adjusted OR (AOR) =0.89; 95% CI AOR = 0.27-2.93; p =0.843). Parents who smoked during the child's first year of life were not at increased risk of having an offspring with CD (OR = 1.94; 95% CI AOR =0.69-5.47; p =0. 203). CONCLUSIONS: No association was found between CD and parental smoking habits during pregnancy or during the child's first year of life. However, further studies with larger numbers of coeliac children are needed.